The discovery of the sweetness of the dipeptide.alpha.-L-aspartyl-L-phenylalanine methylester was reported in 1969 by R. H. Mazur et al (Jour. Amer. Chem. Soc., 91, 2684, 1969). Since then, several methods have been developed for preparing the compound (see, for example, U.S. Pat. Nos. 3,475,403; 3,833,553; 3,798,206; 3,769,333; and 3,933,781).
In U.S. Pat. No. 3,475,403, Mazur et al react N-benzyloxycarbonyl-L-aspartic acid .alpha.-p-nitrophenol and .beta.-benzylester and L-tyrosine methylester, to produce the .beta.-benzyl-N-benzyloxycarbonyl-L-aspartyl-L-tyrosine methylester. In U.S. Pat. No. 3,933,781, L-phenylalanine and N-formyl-L-aspartic anhydride are used to form N-formyl-.alpha.-L-aspartyl-L-phenylalanine which is deformylated and then esterified to obtain the methylester compound.